Binap, (A+-)- → (E)-5-(5-(3-methoxyprop-1-enyl)-4-(1-methylpiperidin-4-ylamino)pyridin-2-ylamino)pyrazine-2-carbonitrile

HRID 384690Notes

Reaction equation

HRID 384690 reaction equation
[CH3:1][O:2][CH2:3]/[CH:4]=[CH:5]/[C:6]1[C:7]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.Br[C:22]1[C:27]([C:28]#[N:29])=[N:26][CH:25]=[CH:24][N:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>O1CCOCC1>[CH3:1][O:2][CH2:3]/[CH:4]=[CH:5]/[C:6]1[C:7]([NH:13][CH:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH2:19]2)=[CH:8][C:9]([NH:12][C:24]2[N:23]=[CH:22][C:27]([C:28]#[N:29])=[N:26][CH:25]=2)=[N:10][CH:11]=1

Participants

6

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 59613524(E)-5-(3-methoxyprop-1-enyl)-N4-(1-methylpiperidin-4-yl)pyridine-2,4-diamineHCID 626739383-Bromopyrazine-2-carbonitrile

Product 1

HCID 59613415(E)-5-(5-(3-methoxyprop-1-enyl)-4-(1-methylpiperidin-4-ylamino)pyridin-2-ylamino)pyrazine-2-carbonitrileYield 3.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (E)-5-(3-methoxyprop-1-enyl)-N4-(1-methylpiperidin-4-yl)pyridine-2,4-diamine (0.090 g, 0.32 mmol), 2-bromo-cyanopyrazine (0.060 g, 0.32 mmol), BINAP (0.007 g, 0.02 mmol), sodium tert-butoxide (0.043 g, 0.45 mmol), tris(dibenzylideneacetone)dipalladium chloroform complex (0.013 g, 0.01 mmol) in dioxane (3 mL) was stirred at room temperature under nitrogen for 10 min, then heated for 30 min at 90° C. under microwave irradiation. The crude reaction mixture was purified by ion exchange on SCX-II acidic resin (1 g) eluting with methanol/dichloromethane (1/1), then 2M ammonia-methanol. The basic fractions were combined and the solvent was removed in vacuo. The crude mixture was purified by preparative thin layer chromatography, eluting with methanol/dichloromethane (1/9), to give the title compound as a yellow solid (0.004 g, 3%).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by ion exchange on SCX-II acidic resin (1 g)
  3. washeluting with methanol/dichloromethane (1/1)
  4. customthe solvent was removed in vacuo
  5. customThe crude mixture was purified by preparative thin layer chromatography
  6. washeluting with methanol/dichloromethane (1/9)

Sources & evidence

ORD record
ord-f46d4de6142e41dca7c6340abd086dab
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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